SPY002-072 for Healthy Volunteers

Recruiting at 2 trial locations

Overseen By Medical Director, Clinical Development

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Spyre Therapeutics, Inc.

Disqualifiers: Drug abuse, Alcoholism, Smoking, others

Compensation: Varies

Number of Visits: 1

Duration: 1 day

56 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but since it is for healthy volunteers, it is likely that participants should not be on any regular medications.

What safety data exists for SPY002-072 or similar treatments in healthy volunteers?

In studies involving healthy volunteers, adverse events (unwanted effects) were reported with both active drugs and placebos. Common issues included headaches, drowsiness, and fatigue, with a higher incidence after repeated doses and in older participants. ^{1 2 3 4 5}

What makes the drug SPY002-072 unique compared to other treatments?

The drug SPY002-072 is unique because it is being tested on healthy volunteers, which suggests it may have a novel mechanism or application not yet explored in existing treatments. However, there is no direct information available about its specific differences from other treatments. ^{6 7 8 9 10}

What is the purpose of this trial?

This is a Phase 1, randomized, double-blind, placebo-controlled, single-dose, first in human safety, tolerability, and pharmacokinetic study of SPY002-072 in healthy participants.

Research Team

Joshua Friedman, MD

Principal Investigator

Spyre Therapeutics

Eligibility Criteria

This trial is for healthy men and women who can commit to staying at the study site for a set period and return for follow-up visits. Participants must be willing to comply with all testing requirements.

Inclusion Criteria

I am a healthy man or woman.

I can attend all required study visits and follow the study rules.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of SPY002-072 or placebo in a dose escalation format

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

40 weeks

Treatment Details

Interventions

• Placebo
• SPY002-072

Trial Overview The trial is testing SPY002-072, a new drug, against a placebo (a substance with no active drug). It's designed to check the safety, tolerability, and how the body processes the drug in those who take it.

Participant Groups

Group I: SAD Cohorts, Experimental Arm Experimental Treatment 1 Intervention

Participants will receive a single dose of SPY002-072 in a dose escalation format

Group II: SAD Cohorts, Placebo Arm Placebo Group 1 Intervention

Participants will receive a single dose of placebo

Who Is Running the Clinical Trial?

Spyre Therapeutics, Inc.

Lead Sponsor

Trials

4

Recruited

270+

Novotech (Australia) Pty Limited

Industry Sponsor

Trials

76

Recruited

7,800+

Dr. John Moller

Novotech (Australia) Pty Limited

Chief Executive Officer

MD and MBA from the University of Oxford

Dr. Judith Ng-Cashin

Novotech (Australia) Pty Limited

Chief Medical Officer since 2023

MD

Altasciences Company Inc.

Industry Sponsor

Trials

18

Recruited

860+

Findings from Research

In a comprehensive review of 54 phase-I studies involving 1015 healthy volunteers over 10 years, the overall incidence of adverse events was found to be 12.8%, with a higher rate for active drugs (13.7%) compared to placebo (7.9%).

Most adverse events were minor, with only 3% classified as severe, and no deaths or life-threatening events reported, highlighting that while adverse events are common in phase-I trials, they are typically not serious.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in phase-I studies: a report in 1015 healthy volunteers. Sibille, M., Deigat, N., Janin, A., et al.[2019]

In a review of 109 clinical studies with 1228 healthy volunteers, 19% reported adverse events during placebo administration, highlighting that even without active treatment, participants can experience side effects.

Adverse events were more common with repeated dosing (28%) and among elderly participants (26%), with headaches, drowsiness, and asthenia being the most frequently reported issues, indicating that placebo effects can significantly influence safety evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. Rosenzweig, P., Brohier, S., Zipfel, A.[2023]

In a five-year analysis of 1,559 healthy volunteers across 142 phase I studies, the overall incidence of adverse events (AEs) was 8.8%, with most AEs being mild or moderate in severity, indicating that while AEs are common, they are generally not severe.

The incidence of AEs was significantly higher in multiple-dose studies compared to single-dose trials, highlighting the importance of study design in assessing the safety profile of active drugs, with a notable increase in AEs on the first day of drug administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in volunteers participating in phase I clinical trials: a single-center five-year survey in 1,559 subjects. Lutfullin, A., Kuhlmann, J., Wensing, G.[2019]

Adverse events (AEs) are reported in 49.1% of trial participants in placebo groups, indicating that these events are quite common and not solely due to the natural progression of conditions.

The prevalence of AEs in placebo groups (6.51%) is higher than in untreated groups (4.25%), suggesting that the nocebo effect may play a significant role in the experience of AEs during clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid overview of systematic reviews of nocebo effects reported by patients taking placebos in clinical trials. Howick, J., Webster, R., Kirby, N., et al.[2022]

The workshop highlighted the potential of using very low dose human studies (microdoses) to assess drug candidates earlier in the development process, which could improve the selection of effective drugs while ensuring volunteer safety.

Incorporating advanced techniques like accelerator mass spectrometry (AMS) and positron emission tomography (PET) in these early human studies could provide valuable data on how drugs are processed in the body, potentially reducing reliance on animal testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early microdose drug studies in human volunteers can minimise animal testing: Proceedings of a workshop organised by Volunteers in Research and Testing. Combes, RD., Berridge, T., Connelly, J., et al.[2019]

The herbal product Buzz, containing 5.4% JWH-018, produced dose-related behavioral effects in mice that were similar to those of marijuana, indicating significant pharmacological activity.

The effects of Buzz were mediated by CB(1) receptors, and the study highlighted the potential public health risks associated with synthetic cannabinoids due to their increased potency and variable composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhalation exposure to smoke from synthetic "marijuana" produces potent cannabimimetic effects in mice. Wiebelhaus, JM., Poklis, JL., Poklis, A., et al.[2021]

A case study revealed that anti-motion sickness transdermal patches marketed as natural contained undeclared active substances, including the antihistamine Diphenhydramine, posing potential health risks.

The analysis also found trace elements, some of which could be toxic, highlighting significant safety concerns regarding the unregulated sale of these patches online.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of medicine in disguise: motion sickness patches sold as medical devices containing active pharmaceutical substances. Gaudiano, MC., Bertocchi, P., De Orsi, D., et al.[2022]

A new gas chromatography-mass spectrometry (GC-MS) method was developed to effectively detect metabolites of JWH-018, a banned substance found in 'K2' or 'Spice', in urine samples from suspected users.

The study identified specific hydrolysis products of JWH-018 metabolites, including 4-hydroxypentyl and 5-hydroxypentyl, which are comparable to existing detection methods, indicating the reliability of this new analytical approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gas chromatography-mass spectrometry of JWH-018 metabolites in urine samples with direct comparison to analytical standards. Emerson, B., Durham, B., Gidden, J., et al.[2021]

Stealth, an adulterant claimed to be undetectable, was found to effectively mask positive drug tests for substances like THC, LSD, and morphine by causing samples to screen negative in immunoassays.

Despite not altering standard urine parameters that indicate adulteration, Stealth's ability to interfere with drug detection poses a significant challenge for drug testing accuracy, as it can convert authentic positive samples into negative results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Stealth adulterant on immunoassay testing for drugs of abuse. Cody, JT., Valtier, S.[2019]

A rapid method using time-of-flight mass spectrometry and direct analysis in real time successfully identified and quantified the synthetic cannabinoid JWH-018 in various 'Spice' products in under five minutes without any sample preparation.

The extraction process yielded clean samples with high recovery rates (97%) and quantified JWH-018 levels in different products, with concentrations ranging from 28 to 90 mg/g of plant material, indicating significant variability in synthetic cannabinoid content across products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification, extraction and quantification of the synthetic cannabinoid JWH-018 from commercially available herbal marijuana alternatives. Dunham, SJ., Hooker, PD., Hyde, RM.[2012]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Adverse events in phase-I studies: a report in 1015 healthy volunteers. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Adverse events in volunteers participating in phase I clinical trials: a single-center five-year survey in 1,559 subjects. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Rapid overview of systematic reviews of nocebo effects reported by patients taking placebos in clinical trials. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Early microdose drug studies in human volunteers can minimise animal testing: Proceedings of a workshop organised by Volunteers in Research and Testing. [2019]

6. Ireland pubmed.ncbi.nlm.nih.gov

Inhalation exposure to smoke from synthetic "marijuana" produces potent cannabimimetic effects in mice. [2021]

7. Italy pubmed.ncbi.nlm.nih.gov

A case of medicine in disguise: motion sickness patches sold as medical devices containing active pharmaceutical substances. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

Gas chromatography-mass spectrometry of JWH-018 metabolites in urine samples with direct comparison to analytical standards. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Effects of Stealth adulterant on immunoassay testing for drugs of abuse. [2019]

10. Ireland pubmed.ncbi.nlm.nih.gov

Identification, extraction and quantification of the synthetic cannabinoid JWH-018 from commercially available herbal marijuana alternatives. [2012]